Oxaliplatin aggravates hepatic oxidative stress, inflammation and fibrosis in a non‑alcoholic fatty liver disease mouse model

Lu,Yulei; Lin,Youzhi; Huang,Xiaoqing; Wu,Shengming; Wei,Jian; Yang,Chun

doi:10.3892/ijmm.2019.4154

Oxaliplatin aggravates hepatic oxidative stress, inflammation and fibrosis in a non‑alcoholic fatty liver disease mouse model

Authors:
- Yulei Lu
- Youzhi Lin
- Xiaoqing Huang
- Shengming Wu
- Jian Wei
- Chun Yang
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Affiliations: Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Pathology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Experimental Pathology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: April 1, 2019 https://doi.org/10.3892/ijmm.2019.4154
Pages: 2398-2408
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oxaliplatin (OXA)‑based chemotherapy is widely used in the treatment of gastrointestinal tumors; however, it is associated with chemotherapy‑associated liver injury. Whether OXA induces liver injury and aggravates the already existing hepatic oxidative stress, inflammation and fibrosis in non‑alcoholic fatty liver disease (NAFLD), and whether these effects can be alleviated by reduced glutathione (GSH) treatment, remains unclear. In the present study, OXA induced acute liver injury in NAFLD mice. Moreover, OXA increased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and decreased the levels of superoxide dismutase and GSH peroxidase in the livers of NAFLD mice. OXA also induced the upregulation of hepatic inflammatory cytokines, such as tumor necrosis factor (TNF)‑α, interferon (IFN)‑γ and interleukin (IL)‑17, in NAFLD mice. Furthermore, collagen fiber deposition in liver tissues was increased and the expression of transforming growth factor (TGF)‑β, α‑smooth muscle actin (SMA) and tissue inhibitor of metallopeptidase (TIMP)‑1 was upregulated in the livers of OXA‑treated NAFLD mice. Treatment with exogenous GSH alleviated OXA‑induced acute liver injury in NAFLD mice, and significantly reduced the levels of ROS, MDA and TNF‑α. However, GSH treatment did not inhibit collagen fiber deposition, although it reduced the levels of IFN‑γ, IL‑17, TGF‑β, α‑SMA and TIMP‑1 in the livers of OXA‑treated NAFLD mice. In conclusion, OXA chemotherapy may induce acute liver injury and aggravate the existing hepatic oxidative stress, inflammation and fibrosis in NAFLD. Treatment of NAFLD mice with exogenous GSH alleviated OXA‑induced liver injury, possibly by ameliorating OXA‑aggravated hepatic oxidative stress and inflammation; it did not, however, attenuate OXA‑aggravated liver fibrosis.

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